Goals are to compare carcinogen metabolism and effects on DNA in three cell types from rats, hamsters and humans. Cells to be studied are pancreatic acinar cells, pancreatic duct cells, and liver cells. Methods to be used include isolation and short term culture of the three cell types from the three species. Carcinogen effects and metabolism will be assessed by (a) alkaline elution analysis of DNA damage, (b) autoradiographic and/or analytical demonstration of repair DNA synthesis in carcinogen treated cells, (c) binding of carcinogen to macromolecules of cell cytoplasm and nuclei, and (d) identification and quantitation of carcinogen metabolites in whole cells and subcellular fractions by HPLC and MS. Carcinogens which will be studied include agaritine, the pyrrolizidine alkaloids, azaserine, N-nitrosobis (2-oxopropyl) amine and related nitrosamines, dimethylnitrosamine, benzo(a)pyrene, and NDelta-(N-methyl-N-nitrosocarbamoyl)-L-ornithine. The data to be obtained should add to our understanding of species differences in initiation of carcinogenesis in pancreas and liver, thereby providing essential background relevant to the cause and prevention of cancer in humans.